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The clinical utility of renal concentrating capacity in polycystic kidney disease.

We studied 177 adult nonazotemic subjects with autosomal dominant polycystic kidney disease (ADPKD) and 123 unaffected family members (NADPKD). In order to assess the factors influencing renal concentrating capacity maximal urinary osmolality (UOsm) after overnight water deprivation and vasopressin was measured. UOsm was reduced in ADPKD (680 +/- 14) compared to NADPKD subjects (812 +/- 13 mOsm/kg). A greater severity of the architectural abnormality as assessed by cyst number and size and remaining volume of normal parenchyma was associated with a greater impairment of renal concentrating capacity. The concentrating defect was present in the youngest ADPKD subjects and the rate of decline of concentrating capacity with age in ADPKD paralleled that in NADPKD subjects. Based on the initial 135 subjects studied, we developed an algorithm for diagnostic screening for ADPKD utilizing blood pressure, serum creatinine and UOsm designed to maximize sensitivity. When applied to a subsequent population of 165 adults, 121 with ADPKD and 44 unaffected relatives, this algorithm would have spared 20% of unaffected subjects from the cost of ultrasound while failing to detect less than 2% of affected subjects. This simple protocol thus offers a rapid and inexpensive way to screen for ADPKD.

Adult↗

Neural networks and physical systems with emergent collective computational abilities.

Computational properties of use of biological organisms or to the construction of computers can emerge as collective properties of systems having a large number of simple equivalent components (or neurons). The physical meaning of content-addressable memory is described by an appropriate phase space flow of the state of a system. A model of such a system is given, based on aspects of neurobiology but readily adapted to integrated circuits. The collective properties of this model produce a content-addressable memory which correctly yields an entire memory from any subpart of sufficient size. The algorithm for the time evolution of the state of the system is based on asynchronous parallel processing. Additional emergent collective properties include some capacity for generalization, familiarity recognition, categorization, error correction, and time sequence retention. The collective properties are only weakly sensitive to details of the modeling or the failure of individual devices.

Animals↗

Reconstruction of two- and three-dimensional images from synthetic-collimator data.

A novel SPECT collimation method, termed the synthetic collimator, is proposed. The synthetic collimator employs a multiple-pinhole aperture and a high-resolution detector. The problem of multiplexing, normally associated with multiple pinholes, is reduced by obtaining projections at a number of pinhole-detector distances. Projections with little multiplexing are collected at small pinhole-detector distances and high-resolution projections are collected at greater pinhole-detector distances. These projections are then reconstructed using the ML-EM algorithm. It is demonstrated through computer simulations that the synthetic collimator has superior resolution properties to a high-resolution parallel-beam (HRPB) collimator and a specially built ultra-high-resolution parallel-beam (UHRPB) collimator designed for our 0.38-mm pixel CdZnTe detectors. It is also shown that reconstructing images in three dimensions is superior to reconstructing them in two dimensions. The advantages of a high-resolution synthetic collimator over the parallel-hole collimators are apparently reduced in the presence of statistical noise. However, a high-sensitivity synthetic collimator was designed which again shows superior properties to the parallel-hole collimators. Finally, it is demonstrated that, for the cases studied, high-resolution detectors are necessary for the proper functionality of the synthetic collimator.

Algorithms↗

Dynamic three-dimensional echocardiography: a new era in ultrasound technology.

The use of noninvasive methods to visualise the heart has had an extraordinary development over the last decade, with echocardiography demonstrating a particularly fast growth. Despite its unquestionable role in the diagnosis of heart disease and in the management of cardiac patients, it does have some limitations, both in the morphological visualisation, as well as in the functional assessment of the heart, such as blood flow, quantification of intracardiac volumes, etc. The recent development of dynamic three-dimensional (3D) echocardiography from two dimensional images has opened new perspectives in the study of cardiac pathophysiology. There are basically two methods of displaying three dimensional data sets: (1) a two-dimensional display from individual selected cut planes (any-plane echocardiography) or from parallel short axis cuts; (2) a volume rendered technique: from any defined cut plane, different algorithms are applied to represent the information in space. There are several potential clinical applications of 3D such as the measurement and serial follow-up of left ventricular volumes; in valvular heart disease (the abnormalities can be delineated more precisely and in greater detail than conventional imaging, including a detailed definition of mitral apparatus in mitral stenosis), in mitral valve prolapse both leaflets can be seen from the left atrial view and in endocarditis it can aid in deciding when and how to intervene; in complex congenital heart disease, such as reconstruction of double outlet right ventricle, left-sided obstructive and regurgitant lesions and subaortic obstructive cases, in atrial and ventricular septal defects, displaying size, geometry and relationships to other structures; another expression of cardiac disorders are blood flow disturbances (visualisation of flows in 3D could allow a better qualitative and quantitative assessment of their size and severity; the pictures so far generated allow a good perception of the size and shape of mitral, aortic and tricuspid regurgitation jets, by examining them from a new perspective, it also has the potential to display the flow convergence zone and quantify the regurgitant volume). Recent studies have clearly demonstrated the feasibility of performing three-dimensional imaging in a variety of cardiac diseases, but continued development of ultrasound technology must be made to improve better image resolution. The prolonged acquisition time is the most important limiting factor that currently restricts the routine use of 3D echocardiography. The development of faster computers will shorten the time needed for image acquisition, postprocessing, and data analysis, contributing to the goal of easy access and wide use. With improvements in computer technology and production of interactive software, 3D echocardiography will provide a dynamic view of the surgical anatomy of the heart. Thus, the three-dimensional reconstruction concept has the potential to and diagnostic assessment of cardiac pathology in every facet.

Cardiovascular Diseases↗

Astigmatic single photon emission computed tomography imaging with a displaced center of rotation.

A filtered backprojection algorithm is developed for single photon emission computed tomography (SPECT) imaging with an astigmatic collimator having a displaced center of rotation. The astigmatic collimator has two perpendicular focal lines, one that is parallel to the axis of rotation of the gamma camera and one that is perpendicular to this axis. Using SPECT simulations of projection data from a hot rod phantom and point source arrays, it is found that a lack of incorporation of the mechanical shift in the reconstruction algorithm causes errors and artifacts in reconstructed SPECT images. The collimator and acquisition parameters in the astigmatic reconstruction formula, which include focal lengths, radius of rotation, and mechanical shifts, are often partly unknown and can be determined using the projections of a point source at various projection angles. The accurate determination of these parameters by a least squares fitting technique using projection data from numerically simulated SPECT acquisitions is studied. These studies show that the accuracy of parameter determination is improved as the distance between the point source and the axis of rotation of the gamma camera is increased. The focal length of the focal line perpendicular to the axis of rotation is determined more accurately than the focal length to the focal line parallel to this axis.

Algorithms↗

Parallel image segmentation using the L4 network.

Each processing element in the outer plexiform layer of the fly's (Musca domestica) compound eye has a single copy of a monopolar cell called L4 whose function is still unknown. This paper proposes that L4 acts as an image segmentor receiving data from the L1 and L2 cell layer above it. The photoreceptor terminals R1 through R6 and L1 and L2 form a cartridge with shunting current inhibition that enhances contrast at the first synaptic contact. The photoreceptors feeding their respective terminals share a common optical axis. What was realized for this entire structure that led up to and included L1 and L2, was that it forms a single processing element which outputs a weighted function based on current shunting between the photoreceptor axon terminals around L1 and L2. Thus the basic biological 'algorithm' that this paper proposes for L1 and L2 involves a summation of the differences between a central reference cell (referred to as Rref) and the six neighboring photoreceptor terminals R1-R6 within the cartridge of L1 and L2. Simulation implementing this simple algorithm on a hexagonal packed matrix in Matlab, suggest that objects with even small differences in intensity with the background, can readily be distinguished from the background. This high pass filter biological model allows edge detection and segmentation, independent of scale in a parallel, modular fashion. Implementation of such a biological algorithm using analog circuitry forms a preprocessing unit that introduces virtually no delay in the processing of image information, in comparison to present DSP techniques, that require iterative approaches and costly computing time.

Algorithms↗

Molecular evidence for parallel evolution of adaptive syndromes in fig-breeding Lissocephala (Drosophilidae).

Afrotropical Lissocephala (Drosophilidae) breed strictly in syconia (figs) of Ficus (Moraceae) and have accordingly evolved specific features including modified female and eggshell morphologies, ovipositing, larval foraging, and mating behaviors. These various traits may exist as two or three alternative states. Each species displays a specific suite of traits so closely coordinated with one another that alternative states of the overall suites of traits can be seen as "adaptive syndromes." Three clear-cut adaptive syndromes can be recognized while two taxonomic lineages (juncta and sanu species groups) are traditionally accepted on the basis of male terminalia. A crucial evolutionary question results from the consideration that ecological clusters and taxonomic groups have conflicting compositions: the three syndromes are found in the juncta group while two of them occur in the sanu group. To resolve this conflict, we present molecular data which provide a robust phylogeny: mitochondrial DNA (12S + 16S ribosomal DNA and cytochrome b) sequence data are in agreement with one another regardless of the algorithm used. All molecular data consistently support male terminalia dichotomy. Such a level of consistency unambiguously indicates that parallel evolution of adaptive syndromes occurred. Thus, homoplasy may affect morphological and behavioral traits concomitantly when these are involved in a network of functional relationships.

Adaptation, Physiological↗

Advanced single-slice rebinning for tilted spiral cone-beam CT.

Future medical CT scanners and today's micro CT scanners demand cone-beam reconstruction algorithms that are capable of reconstructing data acquired from a tilted spiral trajectory where the vector of rotation is not necessarily parallel to the vector of table increment. For the medical CT scanner this case of nonparallel object motion is met for nonzero gantry tilt: the table moves into a direction that is not perpendicular to the plane of rotation. Since this is not a special application of medical CT but rather a daily routine in head exams, there is a strong need for corresponding reconstruction algorithms. In contrast to medical CT, where the special case of nonperpendicular motion is used on purpose, micro CT scanners cannot avoid aberrations of the rotational axis and the table increment vector due to alignment problems. Especially for those micro CT scanners that have the lifting stage mounted on the rotation table (in contrast to setups where the lifting stage holds the rotation table), this kind of misalignment is equivalent to a gantry tilt. We therefore generalize the advanced single-slice rebinning algorithm (ASSR), which is considered a very promising approach for medical cone-beam reconstruction due to its high image quality and its high reconstruction speed [Med. Phys. 27, 754-772 (2000)], to the case of tilted gantries. We evaluate this extended ASSR approach (which we will denote as ASSR+, for convenience) in comparison to the original ASSR algorithm using simulated phantom data for reconstruction. For the case of nonparallel object motion ASSR+ shows significant improvements over ASSR, however, its computational complexity is slightly increased due to the broken symmetry of the spiral trajectory.

Algorithms↗

Monte Carlo methods for small molecule high-throughput experimentation.

By analogy with Monte Carlo algorithms, we propose new strategies for design and redesign of small molecule libraries in high-throughput experimentation, or combinatorial chemistry. Several Monte Carlo methods are examined, including Metropolis, three types of biased schemes, and composite moves that include swapping or parallel tempering. Among them, the biased Monte Carlo schemes exhibit particularly high efficiency in locating optimal compounds. The Monte Carlo strategies are compared to a genetic algorithm approach. Although the best compounds identified by the genetic algorithm are comparable to those from the better Monte Carlo schemes, the diversity of favorable compounds identified is reduced by roughly 60%.

Journal Article↗

A comparison of three electron planning algorithms for a 16 MeV electron beam.

PURPOSE: We report results of a comparison of three electron planning algorithms, an Age-Diffusion Pencil beam algorithm and two (2-D) and three dimensional (3-D) Hogstrom pencil beam algorithms, using simple 2 x 2 cm air and hard bone inhomogeneities and a complex anthropomorphic head and neck phantom. METHODS AND MATERIALS: The simple inhomogeneities have variable dimensions outside the plane of calculation to test the effects of out of plane scattering on 2-D algorithms, compared with dose measured by film below the inhomogeneity in the dose fall-off range. Comparisons are also made of a parotid treatment field for 16 MeV electrons, and the dose measured by high sensitivity thermoluminescent dosimeters in the head and neck phantom. RESULTS: Behind the simple inhomogeneities, the electron algorithms are found to underestimate the dose behind the air cavity by up to 40% and overestimated the dose behind bone by up to 30%. In the head phantom, the presence of inhomogeneities also presents problems for the algorithms, with overestimations of dose of up to 20% found behind bone-tissue interfaces, apparently due to shielding by high density bone. Overestimations of up to 17% are also found beside interfaces parallel to the beam. Underestimations of dose of up to 10% are found on the beam-side of interfaces, due to under-prediction of backscattered electrons. All three investigated algorithms underestimate the dose by up to 20% behind extreme surface curvature. One algorithm is found to underestimate the dose in the falloff region while another overestimates the dose around the 90% isodose. CONCLUSION: Clinicians should be aware of the limitations of their planning systems.

Algorithms↗

Inexpensive, semi-automated system for measuring mechanical properties of soft tissues.

Stiffness and strength are important properties of many tissues, but standard material-testing equipment is expensive, often ill-suited for testing soft tissues, and rarely accessible to biologists. We describe a system built around a microcomputer and an electronic balance which is particularly well-suited for measuring stress and strain in small samples of soft tissue. We use a discarded floppy disk drive as a linear actuator to strain the sample, while an electronic balance measures the tension (used to calculate stress). We give an algorithm for a program to drive a microcomputer which controls the floppy disk drive via its parallel port and records the balance measurements via its serial port. We used this system to obtain stress-strain curves from a sample of latex rubber and a sample of soft insect cuticle. Three tests of the rubber sample gave nearly identical results, with smooth, J-shaped stress-strain curves. The stress-strain curves gave a modulus elasticity value of 1.72 Mpa over the steep, straight region, well within the range for natural latex rubber. We also tested a sample of abdominal cuticle from a caterpillar (Manduca sexta). The caterpillar cuticle had a J-shaped stress-strain curve with a modulus of elasticity of 2.11 Mpa over the steep part of the curve. J. Exp. Zool. 284:374-378, 1999.

Animals↗

Design and fitting of neural network transfer functions.

An algorithm is presented which (a) allows construction of mathematical models involving arbitrary combinations of linear cascades, parallel pathways, and feedback loops, (b) computes a total transfer function of the system, (c) performs a least-squares optimization of model parameters to best fit the model to experimental data, and (d) provides a measure of goodness-of-fit to the data. The technique has been employed to construct and test models of neural networks which mimic a class of responses observed in the cat vestibular nuclei in response to tilt, namely responses which show both a gain increase and progressive phase lag as the stimulation frequency goes from 0.01 to 2 Hz. A network consisting of a simple gain element in parallel with an inhibitory high-pass filtered version of the input provided a satisfactory fit to these data.

Animals↗

Evoked potential techniques in the evaluation of visual function.

Visual evoked potentials (VEPs) can be used in a multitude of ways to assess the various levels of visual processing. The human visual system consists of multiple, parallel channels which process different information, and each channel constitutes a set of sequential processes. An algorithm of sequential steps that can be used to assess visual function is reviewed. The pathophysiology of retinal, anterior visual pathways and retrochiasmal pathways can be objectively evaluated by VEPs.

Adolescent↗

A unified reconstruction framework for both parallel-beam and variable focal-length fan-beam collimators by a Cormack-type inversion of exponential radon transform.

A variety of inversions of exponential Radon transform has been derived based on the circular harmonic transform in Fourier space by several research groups. However, these inversions cannot be directly applied to deal with the reconstruction for fan-beam or variable-focal-length fan-beam collimator geometries in single photon emission computed tomography (SPECT). In this paper, we derived a Cormack-type inversion of the exponential Radon transform by employing the circular harmonic transform directly in the projection space and the image space instead of the Fourier space. Thus, a unified reconstruction framework is established for parallel-, fan-, and variable-focal-length fan-beam collimator geometries. Compared to many existing algorithms, the presented one greatly mitigates the difficulty of image reconstruction due to the complicated collimator geometry and significantly reduces the computational burden of the special functions, such as Chebyshev or Bessel functions. By the well-established fast-Fourier transform (FFT), our algorithm is very efficient, as demonstrated by several numerical simulations.

Algorithms↗

The relationship between traumatic tympanic membrane perforations and pneumatization of the mastoid.

We evaluated the possible relationship between tympanic membrane perforations resulting from blast trauma or slap and pneumatization of the mastoid cells. A total of 25 male patients with tympanic membrane perforations resulting from blast injury (n = 7), slap (n = 17), and football hit (n = 1) and 20 healthy male volunteers without any ear problem had temporal bone computed tomographic scans in the axial plane, parallel to the infraorbitomeatal line, with 2 mm slice thickness and 2-mm intervals using bone algorithm with a ProSpeed Spiral tomography machine. The area of air cells in each slice was measured using trace and area measurement functions of the tomography machine, and by multiplying the resulting area by slice thickness, the volume of each slice was calculated. For each ear, the total of volumes of air cells was calculated by adding the volumes of each slice containing air cells. The calculated volumes of mastoid cells were evaluated by comparing microscopic findings. Both patient and control groups consisted of males, and their ages ranged from 17 to 32 (mean 24.5) years. Microscopic examinations revealed that perforations were frequently located in the lower quadrants and that most of them were less than 3 mm. There were no pars flaccida and marginal perforations. Ossicular chain destruction was noted neither in temporal bone tomographic nor during intraoperative examinations. The mean (+/- SD) volumes of right and left ear mastoid air cells in patient and control groups were 6.92 +/- 2.45 vs. 7.00 +/- 2.59 cm(3) and 9.04 +/- 4.55 vs. 8.95 +/- 4.53 cm(3), respectively, and the differences were not statistically significant. It was found that the level of mastoid pneumatization has no statistically significant effect on tympanic membrane pathologies due to blast or other injuries.

Adolescent↗

Parallel hardware for sequence comparison and alignment.

Sequence comparison, a vital research tool in computational biology, is based on a simple O(n2) algorithm that easily maps to a linear array of processors. This paper reviews and compares high-performance sequence analysis on general-purpose supercomputers and single-purpose reconfigurable, and programmable co-processors. The difficulty of comparing hardware from published performance figures is also noted.

Algorithms↗

Comparison of non parallel immunoassay curves resulting from mixtures of competing antigens.

Relative potency is a measure that has been used for many years to summarize the comparison of dose-response curves in parallel line bioassays. When response curves for two preparations are not parallel the traditional definition of relative potency no longer applies. We review the concept of relative potency and show that, in some situations, it can be given meaning for non-parallel curves as the ratio of biological activity in full strength assay preparations. Under an assumption that non-parallel curves result from the competition of mixtures of antigens for receptor binding sites, estimation of relative potency for non-parallel curves can be accomplished. We show that estimation of models for both parallel curve and response attenuation situations may be accomplished within the framework of generalized linear models. This estimation depends on the ability to deal with non-linear parameters appearing in the link function, and an iterative algorithm depending on direct parameter updates is outlined. The topics discussed are illustrated with the analysis of data from two immunoassays conducted with veterinary vaccines. The models developed here depend in an essential way on the assumption of response attenuation by competing antigens. Our methods may not be appropriate for non-parallel curves caused by other phenomena.

Algorithms↗

Efficient split synthesis for targeted libraries.

We propose a new approach for fabricating more sophisticated combinatorial chemistry libraries via split synthesis and evaluate its potential through extensive simulation. Our algorithmically intensive method promises to reduce the time and materials costs of synthesizing libraries which are (1) too large to synthesize economically by sequential or parallel synthesis, (2) too long or irregular for conventional split synthesis generation techniques, and (3) not used in sufficient quantity to justify the setup costs of array makers. It also encourages the design of more focused and interesting libraries than are typically constructed using split synthesis. Our algorithms automate the design of efficient synthesis procedures for motif-based libraries which are too complex to design by hand. Our software allows the user to select the most desirable tradeoff between minimizing the number of steps in the synthesis process and containing the combinatorial explosion of the number of compounds synthesized.

Algorithms↗